Quantitative changes of gastric mucosal glycoproteins with the gastric damage induced by acetylsalicylic acid (aspirin) in rat have been studied. Gastric injury was easily observed macroscopically within one hour after the oral administration of aspirin. The most striking changes occurred at five hours, and the injury was overcome within nine hours after dosing. The glycoproteins extracted from rat stomack with Tris buffer containing Triton X-100 were fractionated on Bio-Gel A-1.5 m column chromatography and divided into three fractions. The first peak, corresponding to gastric mucus macromolecular neutral and acidic glycoproteins with or without sulphate (Fr.I), was diminished after aspirin administration. A considerable alteration of Fr.I (49% of control) appeared at three hours, and a gradual return to the control value was observed subsequently. The changes in the amount of the glycoproteins were detected before the macroscopical changes of the mucosa. These results suggest that gastric ulceration induced by aspirin may be caused by a deficiency of gastric mucus macromolecular glycoproteins of gastric mucus.